P. Minghetti et al., Comparison of different membranes with cultures of keratinocytes from man for percutaneous absorption of nitroglycerine, J PHARM PHA, 51(6), 1999, pp. 673-678
The permeability barrier function of cell-culture membranes to the permeati
on of nitroglycerine was evaluated to find an alternative to skin from man
for ex-vivo skin-permeation tests.
The membranes were prepared, under submerged conditions, by inducing the gr
owth of keratinocytes, from different donors, on a film of esterified jalur
onic acid for different times (10, 20 and 30 days). Their permeability barr
ier functions were compared with those of some of the most widely used arti
ficial membranes, silicone rubber (Silastic), cellulosic material (Cupropha
n, Millipore HAWP), polysulphone membrane (Supor) and polytetrafluoroethyle
ne membrane (TF PTFE), and with those of biological membranes such as fresh
and frozen skin, stratum corneum and epidermis from man, and hairless mous
e skin. For each membrane the permeation profile was obtained and the flux
was calculated. The permeation profiles for nitroglycerine were similar and
linear in the first 2-3 h for all the synthetic membranes tested except TF
-PTFE. For this membrane the profile was linear throughout the period consi
dered and the amount permeating in 24 h (1603 mu g cm(-2)) was significantl
y lower than those obtained for the other artificial membranes (between 192
6 and 2508 mu g cm(-2)). The amounts permeating through all the biological
membranes in 24 h were in the range 520 to 781 mu g cm(-2), except those fo
r the keratinocyte-culture membranes, which were in the range 1730 to 2553
mu g cm(-2). Prolonging the growth period of cultured keratinocytes did not
affect nitroglycerine permeation.
The findings suggest that these keratinocyte-culture membranes have some ad
vantages-good reproducibility if obtained from the same donor; many membran
es can be obtained from the same donor; the preparation is simple; they can
be handled more easily than traditional cell-culture membranes; and they a
fford constant penetration rates for a longer period than synthetic membran
es. The membranes could be used for preliminary in-vitro permeation studies
.